Is HRAS p.Arg149fs (c.445del) pathogenic?

HRAS p.Arg149fs (c.445del) is classified Uncertain significance in HRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-31). Absent from gnomAD; Associated with Costello syndrome.

What condition is associated with HRAS p.Arg149fs (c.445del)?

HRAS p.Arg149fs (c.445del) is associated with Costello syndrome (ClinVar).

How common is HRAS p.Arg149fs (c.445del) in the general population?

HRAS p.Arg149fs (c.445del) is absent from gnomAD (gnomAD).

HRAS p.Arg149fs

c.445del · rs2133986181 · VCV1390411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Costello syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HRAS
Protein: p.Arg149fs
Coding: c.445del
MANE Select: NM_005343
dbSNP: rs2133986181
Type: Deletion
Location: chr11:533458 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 256 PDB

Full HRAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Costello syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HRAS p.Arg149Gln Uncertain significance ★★ ⚠ same residue
HRAS p.Arg149Trp Uncertain significance ★★ ⚠ same residue
HRAS p.Arg149Leu Uncertain significance ★ ⚠ same residue
HRAS p.Arg149= Likely benign ★ same residue
HRAS p.Leu163fs Pathogenic/Likely pathogenic ★★ same condition
HRAS p.Gly60fs Uncertain significance ★★ same condition
HRAS c.110_111+5del Uncertain significance ★ same condition
HRAS c.112-59_*6-51del Uncertain significance ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/hras-p-arg149fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown